KEGG   DISEASE: H00020Help
Entry
H00020                      Disease                                

Name
Colorectal cancer
Description
Colorectal cancer (CRC) is the second largest cause of cancer-related deaths in Western countries. CRC arises from the colorectal epithelium as a result of the accumulation of genetic alterations in defined oncogenes and tumour suppressor genes (TSG). Two major mechanisms of genomic instability have been identified in sporadic CRC progression. The first, known as chromosomal instability (CIN), results from a series of genetic changes that involve the activation of oncogenes such as K-ras and inactivation of TSG such as p53, DCC/Smad4, and APC. The second, known as  microsatellite instability (MSI), results from inactivation of the DNA mismatch repair genes MLH1 and/or MSH2 by hypermethylation of their promoter, and secondary mutation of genes with coding microsatellites, such as transforming growth factor receptor II (TGF-RII) and BAX. Hereditary syndromes have germline mutations in specific genes (mutation in the tumour suppressor gene APC on chromosome 5q in FAP, mutated DNA mismatch repair genes in HNPCC).
Category
Cancer
BRITE hierarchy
Pathway
Colorectal cancer
MicroRNAs in cancer
Gene
beta-Catenin (mutation) [HSA:1499] [KO:K02105]
K-ras (mutation) [HSA:3845] [KO:K07827]
APC (germline mutation (FAP), somatic mutation) [HSA:10297] [KO:K02085]
DCC (deletion) [HSA:1630] [KO:K06765]
TGF-betaRII (mutation) [HSA:7048] [KO:K04388]
Smad2 (mutation) [HSA:4087] [KO:K04500]
Smad4 (deletion) [HSA:4089] [KO:K04501]
BAX (mutation) [HSA:581] [KO:K02159]
p53 (deletion) [HSA:7157] [KO:K04451]
MLH1 (germline mutation (HNPCC), LOH, promoter hypermethylation) [HSA:4292] [KO:K08734]
MSH2 (germline mutation (HNPCC), LOH, somatic mutation) [HSA:4436] [KO:K08735]
MSH3 (somatic frameshift mutation) [HSA:4437] [KO:K08736]
MSH6 (germline mutation (HNPCC), LOH, somatic frameshift mutation) [HSA:2956] [KO:K08737]
Carcinogen
Mineral oils, untreated and mildly treated
X- and gamma-radiation
Marker
Hemoglobin [HSA:3039 3040 3043]
K-ras (mutation) [HSA:3845]
p53 (mutation) [HSA:7157]
APC (mutation) [HSA:10297]
BAT-26 (mutation)
Drug
Oxaliplatin [DR:D01790]
5-Fluorouracil (5-FU) [DG:DG00687]
Leucovorin (FOLFOX4) [DR:D01211 D04715]
Bevacizumab [DR:D06409]
Irinotecan [DG:DG00726]
Cetuximab [DR:D03455]
Capecitabine [DR:D01223]
Comment
ICD-O: 8140/3, Tumor type: Adenocarcinoma
Other DBs
ICD-10: 
MeSH: 
Reference
PMID:15000146 (gene, tumor type)
  Authors
Grady WM.
  Title
Genomic instability and colon cancer.
  Journal
Cancer Metastasis Rev 23:11-27 (2004)
Reference
PMID:11477132 (tumor type)
  Authors
Houlston RS.
  Title
What we could do now: molecular pathology of colorectal cancer.
  Journal
Mol Pathol 54:206-14 (2001)
Reference
PMID:16555243 (gene)
  Authors
Soreide K, Janssen EA, Soiland H, Korner H, Baak JP.
  Title
Microsatellite instability in colorectal cancer.
  Journal
Br J Surg 93:395-406 (2006)
Reference
PMID:12621137 (gene)
  Authors
Lynch HT, de la Chapelle A.
  Title
Hereditary colorectal cancer.
  Journal
N Engl J Med 348:919-32 (2003)
Reference
PMID:15310786 (gene)
  Authors
Mehlen P, Fearon ER.
  Title
Role of the dependence receptor DCC in colorectal cancer pathogenesis.
  Journal
J Clin Oncol 22:3420-8 (2004)
Reference
PMID:9498901 (carcinogen)
  Authors
Tolbert PE.
  Title
Oils and cancer.
  Journal
Cancer Causes Control 8:386-405 (1997)
Reference
PMID:15070562 (carcinogen)
  Authors
Berrington de Gonzalez A, Darby S.
  Title
Risk of cancer from diagnostic X-rays: estimates for the UK and 14 other countries.
  Journal
Lancet 363:345-51 (2004)
Reference
PMID:15929776 (marker)
  Authors
Ouyang DL, Chen JJ, Getzenberg RH, Schoen RE.
  Title
Noninvasive testing for colorectal cancer: a review.
  Journal
Am J Gastroenterol 100:1393-403 (2005)
Reference
PMID:15738983 (marker)
  Authors
Davies RJ, Miller R, Coleman N.
  Title
Colorectal cancer screening: prospects for molecular stool analysis.
  Journal
Nat Rev Cancer 5:199-209 (2005)
Reference
(drug)
  Authors
McPhee SJ, Papadakis MA, Tierney LM (ed).
  Title
Current Medical Diagnosis & Treatment 2007, Forty-Sixth Edition
  Journal
The McGraw-Hill Companies, Inc. (2007)

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